Synthetic biology: tools to design, build, and optimize cellular processes

Abstract

The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of synthetic biology into three tiers: (1) the process units and associated streams of the central dogma, (2) the intrinsic regulatory mechanisms, and (3) the extrinsic physical and chemical environment. Efforts at each of these three tiers attempt to control cellular systems and take advantage of emerging tools and approaches. Ultimately, it will be possible to integrate these approaches and realize the vision of integrative synthetic biology when cells are completely rewired for biotechnological goals. This review will highlight progress towards this goal as well as areas requiring further research.

Figure 1

The central dogma with regulatory and environmental influences acting upon the process. The two central dogma process units (transcription and translation) and the three process streams (DNA, RNA, and protein) are depicted. These units and streams are all subject to control by both internal, regulatory and external, environmental conditions. These influences alter the central dogma process and regulatory mechanisms. Large bold arrows are used to indicate that proteins are the major workhorses of the cell, participating both in regulatory mechanisms and responding to the environment. Whether the system of interest is a signaling cascade or metabolic pathway, proteins are essential components and must become well understood and modifiable to bring about ground-up cellular optimization. Synthetic biology is developing tools to modify and control each unit and stream in this process.

Figure 2

Interaction of components illustrating synthetic biology at the three tiers. (a) Canonical signalling pathway depicting a tier three ligand-receptor binding event that induces a tier two phosphorylation cascade which subsequently alters a promoter at the first tier. (b) Canonical allosteric protein inhibition by a molecule downstream in the pathway. The inhibition binding event is a tier three interaction which results in a tier two alteration in the pathway “set point.” (c) Hypothetical signalling pathway in which a signal molecule alters an initiation factor at tier three which then changes the tier two protein translation set point.